Healthcare (Commonwealth Union) – Scientists believe monoclonal antibodies—produced by cloning a cell that generates a specific antibody—could offer a solution to the rising issue of antimicrobial resistance.
A team of researchers, led by scientists from the University of Cambridge, has developed a monoclonal antibody therapy using genetically modified mice. This treatment could help prevent infections caused by Acinetobacter baumannii, a bacterium often linked to hospital-acquired infections, especially in Asia.
Researchers of the study pointed out that Acinetobacter baumannii can lead to severe respiratory illnesses and sepsis, particularly in vulnerable patients such as newborns with underdeveloped immune systems. It is commonly transmitted through contaminated surfaces, medical devices, and person-to-person contact. In recent years, infections caused by strains of this bacterium resistant to nearly all available antibiotics have become widespread.
Professor Stephen Baker, from the Cambridge Institute of Therapeutic Immunology and Infectious Disease, pointed out that A. baumannii has a strong ability to adhere to medical equipment. Professor Baker, further indicated that when people have a compromised immune system, they are at risk of contracting aggressive pneumonia, often requiring ventilation—and, in many cases, the infection is acquired directly from the ventilator itself.
“The bacteria are naturally resistant to many antimicrobials, but as they’re now found in hospitals, they’ve acquired resistance to almost everything we can use. In some hospitals in Asia, where the infections are most common, there isn’t a single antibiotic that will work against them. They’ve become impossible to treat.”
In a study appearing recently in Nature Communications, researchers used transgenic mice—genetically modified to possess a human-like immune system that produces human antibodies instead of mouse antibodies—to generate monoclonal antibodies. The study demonstrated that these antibodies could successfully prevent infections caused by Acinetobacter baumannii strains obtained from clinical samples.
The researchers highlighted the fact that monoclonal antibodies are an expanding field in medicine, commonly employed to treat conditions such as cancer (e.g., Herceptin for certain breast cancers) and autoimmune diseases (e.g., Humira for rheumatoid arthritis, psoriasis, Crohn’s disease, and ulcerative colitis).
Typically, monoclonal antibodies are either derived from patients who have recovered from an infection or engineered to target specific antigens. For instance, monoclonal antibodies designed to bind to the ‘spike protein’ of the SARS-CoV-2 virus were explored as a treatment for COVID-19.
In contrast, the Cambridge University team exposed transgenic mice to the outer membrane of A. baumannii bacteria, prompting an immune response. From there, they isolated nearly 300 different antibodies and evaluated their ability to recognize live bacteria, ultimately identifying mAb1416 as the most effective monoclonal antibody.
Professor Baker stated that with this approach, they do not expose the mice to live bacteria. Instead, they immunize them using different components and allow their immune system to determine which ones to target with antibodies. Since these mice have human-like immune systems, there is no need to modify the antibodies for use in humans.
The researchers treated mice with the monoclonal antibody mAb1416 and, 24 hours later, exposed them to Acinetobacter baumannii bacteria isolated from a child with sepsis in an ICU. The results showed that mice treated with mAb1416 had a significantly lower bacterial load in their lungs 24 hours later compared to untreated mice.
The bacterial isolates used for producing and testing the monoclonal antibodies were collected from patients in Ho Chi Minh City, Vietnam. However, the isolate used to evaluate mAb1416 was taken a decade after the others. This is a crucial finding, as it demonstrates that mAb1416 was effective against A. baumannii strains that may have evolved over time as indicated by the researchers.
Professor Baker says “Using this technique, you can take any bacterial antigen or cocktail of antigens, rather than waiting for somebody that’s recovered from a particular infection – who you assume has developed an appropriate antibody response – give it to the mice and extract the antibodies you think are the most important.”
